Pantothenic acid is a commercially significant vitamin which is used in cosmetics, medicine, human nourishment and in animal nourishment.
Pantothenic acid can be produced by chemical synthesis or biotechnologically by the fermentation of suitable microorganisms in suitable nutrient solutions. The advantage of the biotechnological production with microorganisms resides in the formation of the desired stereoisomeric D-form of pantothenic acid.
Various types of bacteria such as, for example, Escherichia coli, Corynebacterium erythrogenes, Brevibacterium ammoniagenes and also yeasts such as, for example, Debaromyces castellii can produce D-pantothenic acid in a nutrient solution containing glucose, DL-pantoic acid and .beta.-alanine, as is shown in EP-A 0,493,060. EP-A 0,493,060 also shows that the formation of D-pantothenic acid is improved in the case of Escherichia coli by amplification of pantothenic-acid biosynthetic genes by means of the plasmids pFV3 and pFV5.
EP-A 0,590,857 is relative to strains of Escherichia coli which carry resistances against various antimetabolites such as, salicylic acid, .alpha.-ketobutyric acid, .beta.-hydroxyaspartic acid, etc. and produce D-pantoic acid and D-pantothenic acid in a nutrient solution containing glucose and .beta.-alanine. EP- 0,590,857 also describes that the production of D-pantoic acid and D-pantothenic acid in E. coli can be improved by amplification of pantothenic-acid biosynthetic genes (not defined in detail), from E. coli which are contained on the plasmid pFV31.
Moreover, WO 97/10340 shows that the production of pantothenic acid can be further increased in mutants of Escherichia coli forming pantothenic acid by elevating the activity of the enzyme acetohydroxy-acid synthesis II, an enzyme of valine biosynthesis.